AN IN-VIVO P-31 MAGNETIC-RESONANCE SPECTROSCOPY STUDY OF URIDINE EXCESS IN RATS FED OROTIC-ACID

Spatially localized P-31 NMR spectroscopy was used to assay in vivo th e liver of intact rats fed erotic acid (OA) in a diet which produces h epatic steatosis. Twenty-three sets of multiple volume spectra were ob tained from twenty-one 265- to 315-g female rats after 0-9 days of fee ding either a 1% OA/64% sucrose diet (12 rats) or a 65% sucrose contro l diet (9 rats). The intensity of the in vivo diphosphodiester resonan ce ascribed to UDP-hexos(amin)es increased and the phosphomonoester re sonance decreased in intensity prior to fatty infiltration. High resol ution NMR spectroscopy of extracts of these livers indicated that the UDP-hexos(amin)e peak included four different UDP-sugars including UDP -N-acetylglucosamine (UDP-glcNAc), and that lower phosphocholine (P-Ch o) accounted for the lower phosphomonoester resonance in vivo. Increas ed UDP-glcNAc is thought to reflect impaired lipoprotein glycosylation as a mechanism for hepatic steatosis in erotic acid feeding. P-Che de ficiency has been shown to be due to an increased rate of phosphatidyl choline synthesis. Low P-Cho concentration has been shown to be associ ated with lipid accumulation in a choline-deficient diet, but was not previously associated with hepatic steatosis in OA feeding. Changes in phosphorus metabolites were observed 2 days prior to the development of fatty liver, HPLC assay of uridine nucleotides showed a good correl ation between magnetic resonance spectroscopy and HPLC quantitation. I n this study there were two biochemical correlates of impaired hepatic lipid secretion detectable by in vivo assay with P-31 NMR spectroscop y. This method has application for noninvasive assays in ornithine tra nscarbamylase-deficient patients. (C) 1995 Academic Press, Inc.